title: Zebrafish as a novel model to assess Na+/K(+)-ATPase-related neurological disorders.
abstract: Modeling neurological disorders using zebrafish increases rapidly as this model system allows easy access to all developmental stages and imaging of pathological processes. A surprising degree of functional conservation has been demonstrated between human genes implicated in neurodegenerative diseases and their zebrafish orthologues. Zebrafish offers rapid high throughput screening of therapeutic compounds and live imaging of pathogenic mechanisms in vivo. Several recent zebrafish studies functionally assessed the role of the sodium-potassium pump (Na(+)/K(+)-ATPase). The Na(+)/K(+)-ATPase maintains the electrochemical gradients across the plasma membrane, essential for e.g. signaling, secondary active transport, glutamate re-uptake and neuron excitability in animal cells. Na(+)/K(+)-ATPase mutations are associated with neurological disorders, where mutations in the Na(+)/K(+)-ATPase α2 and α3 isoforms cause Familial hemiplegic migraine type 2 (FHM2) and Rapid-onset dystonia-parkinsonism (RDP)/Alternating hemiplegic childhood (AHC), respectively. In zebrafish, knock-down of Na(+)/K(+)-ATPase isoforms included skeletal and heart muscle defects, impaired embryonic motility, depolarized Rohon-beard neurons and abrupt brain ventricle development. In this review, we discuss zebrafish as a model to assess Na(+)/K(+)-ATPase isoform functions. Furthermore, studies investigating proteomic changes in both α2- and α3-isoform deficient embryos and their potential connections to the Na(+)/K(+)-ATPase functions will be discussed.
authors.affiliation: Centre for Membrane Pumps in Cells and Disease-PUMPKIN, Danish National Research Foundation, Copenhagen, Denmark; Aarhus University, Department of Biomedicine, Ole Worms Allé 3, Building 1171, DK-8000 Aarhus, Denmark; Aarhus University, Department of Molecular Biology and Genetics, Gustav Wieds Vej 10, Building 3135, DK-8000 Aarhus, Denmark.
authors.forename: Canan
authors.initials: C
authors.lastname: Doğanli
authors.forename: Claus
authors.initials: C
authors.lastname: Oxvig
authors.forename: Karin
authors.initials: K
authors.lastname: Lykke-Hartmann
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D020325:Migraine with Aura / Q000175:diagnosis / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009422:Nervous System Diseases / Q000175:diagnosis* / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish
chemical_list: D000254:Sodium-Potassium-Exchanging ATPase
keywords: Brain ventricle development; Familial hemiplegic migraine type 2 (FHM2); Na(+)/K(+)-ATPase; Rapid-onset dystonia-parkinsonism (RDP); Zebrafish